This program of investigation focuses on the genetics of Specific Language Impairment. We investigate longitudinal behavioral language phenotypes within a multi-gene developmental model involving a complex interaction of genetics, developmental brain changes, and overlapping phenotypes that intertwine throughout childhood with enduring individual differences in performance levels. Three previous award cycles have generated an empirical archive of proband and family data that is unique for the detailed documentation of longitudinal growth patterns across multiple indices of language, non-word repetition, reading, and speech sound acquisition. The archive previews a consistent picture for children with SLI of delayed onset of language, lower language levels that persist through adolescence, parallel growth trajectories to unaffected children although at lower levels of performance, and grammatical limitations out of sync with other dimensions of language although also following the growth trajectories of unaffected children. Family members show an elevated rate of affectedness. Co-morbidity of language and reading impairments is evident in affected children. Candidate gene linkage analyses suggest differential gene influences for language, speech, and reading impairments. In the proposed award cycle we will address some of the challenges inherent in these early genetic investigations of SLI. One is that current methods of phenotyping collapse across age levels, thereby obscuring potential developmental effects. The second is that the linguistic indicators are either relatively narrowly defined or broadly defined by omnibus language tests, making it difficult to interpret the ways in which particular genetic effects would impact the emerging linguistic system. The third is that sample sizes yield low power for detection of potential gene interactions. In the proposed award cycle our specific aims are: (1) Compile a behavioral database of probands, controls, and family members to be used for developing growth phenotypes in language, reading, speech, and non-word repetition. (2) To investigate the relationships among grammatical markers, vocabulary, omnibus language test, verbal memory, reading and nonverbal intelligence measures in children with SLI and controls and how the relationships change over time. (3) Carry out molecular genetic analyses. The results will document growth trajectories of affected and unaffected children, to provide a longitudinal perspective on the outcomes of SLI;will clarify the nature of the language phenotype(s) and relationships with related abilities;and will identify potential genes of influence for the developmental trajectories across dimensions of language, reading and non-word repetition. The results would have implications for the development of clinical interventions that are benchmarked to onset of language, expected rates of change, and expected associations of language outcomes with reading, non-word repetition, nonverbal intelligence, and mother's education. PUBLIC HEALTH RELEVANCE: Children with Specific Language Impairment (SLI) do not outgrow early delays in language acquisition and there are indications that the cause is genetic in origin. This program of investigation documents language growth as a phenotype for genetics analyses, to identify possible genetic contributions to language acquisition and language impairments, as well as reading and speech sound disorders (SSD). The results would improve interventions by documenting the need for long-term intervention and identifying when particular dimensions of language, speech and reading are most likely to improve.